Pediatric end-stage renal disease: Heart as a target
2002; Elsevier BV; Volume: 141; Issue: 2 Linguagem: Inglês
10.1067/mpd.2002.126921
ISSN1097-6833
Autores Tópico(s)Heart Failure Treatment and Management
ResumoSee related article, p 191. Chronic hemo- and peritoneal dialysis have been established as live-saving and live-sustaining modalities for the treatment of patients with end-stage renal disease (ESRD). Hundreds of thousands of persons are alive today as a result of receiving dialysis. Approximately 1000 new patients enter pediatric ESRD programs annually, and approximately 5000 children are receiving maintenance dialysis in the United States. Despite the widespread availability and advancements in dialysis, the expected remaining lifetime for children with ESRD remains low, between 35% and 47% of that of an age- and race-matched US population.1The USRDS 1998 Annual Report Causes of death.Am J Kidney Dis. 1998; 32: 81-88Google Scholar Throughout the last decade, it was realized that the major killer in adult chronic dialysis patients was not uremia per se but cardiovascular disease (CVD). In 1998, the National Kidney Foundation Task Force on CVD declared an epidemic of cardiac disease in patients with chronic renal disease. A cardiac cause accounted for almost half of all causes of death and the rate of death was approximately 10 to 20 times higher than in the general population.2Task Force on Cardiovascular Disease Special report from the National Kidney Foundation.Am J Kidney Dis. 1998; 32: 1-121PubMed Google Scholar It was even more alarming that CVD mortality was exceptionally high in young adults (25-34 years old) who were receiving chronic dialysis, more than 100 times higher than in the comparably-aged general population. The report from the Task Force also raised questions regarding pediatric patients on dialysis: (1) Do they have cardiac disease? (2) Do they die from cardiac disease? and (3) If so, how significant is this problem? Cardiac disease mortality is low in the general pediatric population and accounts for <3% of all causes of death.3Annual Summary of Vital Statistics 2000.Pediatrics. 2001; 108: 1241-1255Crossref PubMed Scopus (131) Google Scholar Yet, CVD mortality is the second leading cause of death in children with ESRD, accounting for almost 25% of all deaths.4The USRDS 2001 Annual Data Report Pediatric ESRD.Am J Kidney Dis. 2001; 38: 107-116Google Scholar It is important to note that the data on cause of death do not necessarily reflect risk. To compare the risk of death, it is necessary to know the number of patients at risk during the interval in which mortality is assessed. In this issue of The Journal, Parekh et al,5Parekh RS Carrol CE Wolfe RA Port FK Cardiovascular death in children and young adults with end-stage kidney disease.J Pediatr. 2002; 141: 191-197Abstract Full Text Full Text PDF PubMed Scopus (384) Google Scholar using the United State Renal Data System database, present astonishing evidence that children and young adults in whom ESRD developed during childhood have a cardiac death rate approximately 1000 times higher than that of the general pediatric population. To understand why pediatric patients and young adults with ESRD die prematurely from cardiovascular complications, the risk factors for CVD morbidity and mortality must be identified. In adult patients with chronic renal disease, coronary artery disease and left ventricular hypertrophy (LVH) were identified as two conditions with very high prevalence that contribute to cardiac failure, symptomatic ischemic heart disease, and, eventually, increased CVD mortality.2Task Force on Cardiovascular Disease Special report from the National Kidney Foundation.Am J Kidney Dis. 1998; 32: 1-121PubMed Google Scholar One of the reasons for the high rate of these cardiovascular complications is the overrepresentation of classical risk factors for CVD in patients with ESRD: diabetes, hypertension, hyperlipidemia, and hyperhomocysteinemia are more prevalent in dialysis patients than in the nonuremic population. A majority of adults have ESRD as a complication of diabetes or generalized atherosclerosis. Often, cardiac disease is already well established at the onset of ESRD in these patients. Children have neither diabetes nor symptomatic atherosclerosis at the time of starting chronic dialysis; however, they still die from CVD while receiving chronic dialysis. What, then, are the factors contributing to the development of cardiovascular events in these young patients? Unfortunately, children with ESRD share many similar risk factors for CVD with adults: ~50% to 75% of uremic children are hypertensive and as many as 70% to 90% develop hyperlipidemia during chronic dialysis.6Loirat C Ehrich JHH Geerlings W Jones EHP Landais P Mallick NP et al.Report on management of renal failure in children in Europe, XXIII, 1992.Nephrol Dial Transplant. 1994; 9: 26-40PubMed Google Scholar, 7Querfeld U Salusky IB Nelson P Fine RN Hyperlipidemia in pediatric patients undergoing peritoneal dialysis.Pediatr Nephrol. 1988; 2: 447-452Crossref PubMed Scopus (41) Google Scholar In addition to these traditional risk factors, children receiving chronic dialysis may amplify their cardiovascular risk because of uremia-related factors including anemia, hemodynamic overload, hypoalbuminemia, inadequate dialysis, chronic inflammation, and hyperparathyroidism. Thus, the combination of traditional and uremia-related risk factors might be the reason for the development and acceleration of cardiac disease in pediatric ESRD. The presence of hypertension, hypervolemia, and anemia can explain the high prevalence and persistence of LVH, which we reported to be present in as much as 75% of children receiving dialysis.8Mitsnefes MM Daniels SR Schwartz SA Khoury P Meyer RA Strife CF Severe left ventricular hypertrophy in pediatric dialysis: prevalence and predictors.Pediatr Nephrol. 2000; 14: 898-902Crossref PubMed Scopus (191) Google Scholar Increased left ventricular mass initially has the beneficial effect of reducing left ventricular wall stress, but long-standing cardiac hypertrophy ultimately leads to maladaptive LVH with decreased capillary density, coronary reserve and subendocardial perfusion, and the development of myocardial fibrosis. All this leads to myocyte death, with diastolic and systolic dysfunction, and eventually may lead to cardiac failure and death. Although symptomatic coronary artery disease is not frequent in children, the atherogenic process might well begin in childhood. Early atherosclerotic lesions were reported in association with cigarette smoking and high cholesterol level in the Pathological Determinants of Atherosclerosis in Youth study.9Relationship of atherosclerosis in young men to serum lipoprotein cholesterol concentrations and smoking A preliminary report from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group.JAMA. 1990; 264: 3018-3024Crossref PubMed Scopus (570) Google Scholar In the Bogalusa Autopsy Study, Berenson et al10Berenson GS Srinivasan SR Bao W Newman 3rd, WP Tracy RE Wattigney WA Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study.N Engl J Med. 1998; 338: 1650-1656Crossref PubMed Scopus (3224) Google Scholar showed that atherosclerosis might be present in children and young adults (without chronic renal disease) and is associated with traditional risk factors such as systolic hypertension and hyperlipidemia. Given that these risk factors are strongly present in young patients receiving dialysis, it is reasonable to consider that progressive coronary artery disease might develop in these patients. Goodman et al11Goodman WG Goldin J Kuizon BD Chun Yoon Gales B Sider D et al.Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis.N Engl J Med. 2000; 342: 1478-1483Crossref PubMed Scopus (2491) Google Scholar recently presented evidence for the development of coronary artery disease in young adults with ESRD. By using electron-beam computed tomography, they showed that 88% of men and women 20 to 30 years old had a progressive coronary artery calcification while receiving chronic dialysis. More importantly, most of these patients initiated chronic dialysis as children or adolescents with an average age of 13 ± 4 years. Finally, Portman et al12Portman RJ Hawkins E Verani R Premature atherosclerosis in pediatric renal patients: report of the Southwest Pediatric Nephrology Study Group [abstract].Ped Res. 1991; 29: 349Google Scholar analyzed 40 autopsy reports from children who died during the time they were receiving chronic dialysis. They found that 78% of these children had mild-to-severe atherosclerosis of the cardiac arteries. One hopeful observation in the report by Parekh et al5Parekh RS Carrol CE Wolfe RA Port FK Cardiovascular death in children and young adults with end-stage kidney disease.J Pediatr. 2002; 141: 191-197Abstract Full Text Full Text PDF PubMed Scopus (384) Google Scholar is the fact that cardiac death decreased significantly after renal transplantation. Transplant recipients had a 78% lower risk of cardiac death compared with patients who were receiving dialysis. Despite this sense of optimism, Parekh et al pointed out that death from CVD remains markedly higher than in the general pediatric population and continues to be one of the main causes of death in children and young adults after renal transplantation. We should remember that, despite dramatic improvement of renal function and elimination of many risk factors for CVD in children on dialysis, the state of renal transplantation is one of chronic renal insufficiency. Transplant recipients are not free from multiple complications of renal failure and immunosuppressive agents. Indeed, the report from North American Pediatric Renal Transplant Cooperative Study demonstrates that the prevalence of hypertension in pediatric renal allograft recipients is between 70% and 80%.13Baluarte HJ Gruskin AB Ingelfinger JR Stablein D Tejani A Analysis of hypertension in children post renal transplantation: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).Pediatr Nephrol. 1994; 8: 570-573Crossref PubMed Scopus (100) Google Scholar As a consequence, LVH remains common (50%-80%) in these children.14Matteucci MG Giordano U Calzolari A Turchetta A Santilli A Rizzoni G Left ventricular hypertrophy, treadmill tests, and 24-hour blood pressure in pediatric transplant patients.Kidney Int. 1999; 56: 1566-1570Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar, 15Mitsnefes MM Schwartz SM Daniels SR Kimball TR Khoury P Strife CF Changes in left ventricular mass index in children and adolescents after renal transplantation.Pediatr Transplant. 2001; 5: 279-284Crossref PubMed Scopus (70) Google Scholar Hyperlipidemia may not improve after renal transplantation, with reported prevalence of about 50%.16Silverstein DM Palmer J Polinsky MS Braas C Conley SB Baluarte HJ Risk factors for hyperlipidemia in long-term pediatric renal transplant recipients.Pediatr Nephrol. 2000; 14: 105-110Crossref PubMed Scopus (60) Google Scholar Thus, pediatric renal transplantation must also be considered in a state of ongoing high risk for the development and progression of CVD. Our knowledge of the clinical epidemiology of cardiovascular disease in pediatric chronic renal disease is still rudimentary. The paper by Parekh et al5Parekh RS Carrol CE Wolfe RA Port FK Cardiovascular death in children and young adults with end-stage kidney disease.J Pediatr. 2002; 141: 191-197Abstract Full Text Full Text PDF PubMed Scopus (384) Google Scholar is a necessary step to help in understanding the magnitude of this problem. It is also an important step in the search for determinants that can be altered or eliminated to reduce or prevent CVD in pediatric ESRD. The authors' message is clear: long-term dialysis is a significant risk factor for increased CVD mortality in children and young adults. This underscores the importance of preemptive renal transplantation and expedited transition from dialysis to transplantation as a preferred method of renal replacement therapy in children with ESRD. As a population without preexisting symptomatic cardiac disease, children with chronic renal disease have a significant advantage from aggressive attempts at prevention, diagnosis, and treatment of CVD. The question is when do we need to start those attempts? There are reports that cardiac and vascular abnormalities begin to develop at earlier stages of chronic renal insufficiency.17Kari J Donald AE Vallance DT Bruckdorfer KR Leone A Mullen MJ et al.Physiology and biochemistry of endothelial function in children with chronic renal failure.Kidney Int. 1997; 52: 468-472Abstract Full Text PDF PubMed Scopus (209) Google Scholar, 18Mitsnefes MM Kimball TR Khoury P Daniels SR Cardiac status in children with chronic renal disease [abstract].J Am Soc Nephrol. 2001; 12: 0451Google Scholar But exactly when these abnormalities first appear in the course of renal failure is not known. Prospective studies in this area are lacking and, hence, our understanding of the mechanisms of progression of cardiac or vascular abnormalities under these conditions is limited. It is possible that mild-to-moderate renal insufficiency, when there is no yet need for dialysis is the optimal time during which identification of modifiable risk factors and early intervention might lead to the prevention of CVD. Cardiovascular mortality in children and young adults with end-stage kidney diseaseThe Journal of PediatricsVol. 141Issue 2PreviewObjective: To analyze cardiovascular death in a national end-stage renal disease (ESRD) population. Study design: This retrospective, observational study with data from the US Renal Data Systems analyzed 1380 deaths from 1990 to 1996 among patients who started ESRD therapy as children and died before 30 years of age. Results: Percentage of cardiac deaths (n = 311) varied by age and was higher among black patients (0-4 years, 36%; 5-9 years, 18%; 10-14 years, 35%; 15-19 years, 22%; 20-30 years, 32%) than white patients (18%, 12%, 17%, 14%, and 23%, respectively). Full-Text PDF
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